Dabrafenib is a benzene sulfonamide thiazole compound and is a selective BRAF inhibitor. Results of the Phase I/II clinical trials show Dabrafenib has therapeutic activities and an acceptable safety profile in patients with BRAFV600E-mutan melanoma. The chemical name of Dabrafenib methanesulfonate is N-[3-[5-(2-amino-4-pyrimidinyl)-2-(tert-butyl)-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzene sulfonamide methanesulfonate; the molecular formula: C24H24F3N5O5S3; molecular weight: 615.7; and chemical structure as follows:

Patent documents WO2009/137391 and CN200980126781.6 (incorporated into the present application by reference) disclosed identification, preparing process and uses of Dabrafenib methanesulfonate. To be specific, examples 58d and 58e disclosed Dabrafenib methanesulfonate and its preparation methods, and provided its 1HNMR data, but did not provide characterization data in relation to its physical state. Moreover, the patent documents also disclosed that Dabrafenib methanesulfonate exhibited inhibitory effects on one or more Raf-family kinases.
In addition, patent document WO2012/148588A2 (incorporated into the present application by reference) disclosed Raman, XRPD and DSC/TGA analytical data of Dabrafenib methanesulfonate that was mentioned in WO2009/137391. For convenience, the crystal form prepared according to examples 58d and 58e in WO2009/137391 and CN200980126781.6 hereinafter is referred as to “the Known Crystal Form I”.
In the present research, it was discovered that the Known Crystal Form I has the following defects: it readily converts to free base in water or other aqueous system(s), thus unable to maintain its original crystalline form. In pharmaceutical processes, this change may result in changes in nature and bioavailabilities of formulations.
Therefore, there is a need to discover new crystal forms of Dabrafenib methanesulfonate with good purity, improved thermodynamic stability in water or aqueous system(s) and better suitability for the pharmaceutical application.